The meetings in Havana follow the historic decision by US President Barack Obama and Cuban leader Raul Castro in December to seek normal diplomatic relations.
"In Cuba, we are ending a policy that was long past its expiration date," Obama said in his annual State of the Union speech late Tuesday, urging the US Congress to lift the decades-old embargo.
"When what you have done doesn't work for fifty years. It's time to try something new," he said.
Cuba will be represented by Josefina Vidal, director of the foreign ministry's US affairs, for the two days of talks.
"We hope to establish civilized relations between countries that have different political concepts, but which can get along while respecting these differences," an unnamed Cuban foreign ministry official told pro-government website cubadebate.Cu.
The first day of talks in Havana's Convention Center will focus on migration, an issue for both nations as Cuba has seen an exodus of Cubans to nearby Florida over the years.
The Cuban official said Havana will express its concerns about a US policy that gives Cubans quick access to permanent residency when they set foot on US soil.
But a senior US official said there were "no plans to change US policy," which must be modified by Congress.
Jacobson will participate in Thursday's negotiations on reopening embassies, which closed after relations were severed in 1961.
The US side wants Cuba to reaccredit its diplomats, lift travel restrictions for them within the island, ease shipments to the US mission and lift a cap on personnel.